Candida species are a commonly seen form of yeast present in the gastrointestinal tract, mucosa, and skin of healthy individuals as a part of normal flora. When the immune defense of a host is deteriorated, Candida spp. can cause life-threatening disorders by invading tissues. Candida albicans is the most commonly isolated species of nearly all forms of candidiasis (Hazen & Howell (2003) Manual of Clinical Microbiology, Murray et al. (eds), 8th Ed. Washington D.C.: ASM Press, pp 1693-711).
Biofilm formation plays an essential role in the pathogenicity of C. albicans (Seneviratne, et al. (2008) Oral Dis. 14:582-90; Richard, et al. (2005) Eukaryot. Cell 4:1493-502). Biofilm is a cell population that is surrounded by an extracellular matrix composed of yeast cells and filaments; it has a relationship with the surface and exhibits different phenotypic features than planktonic cells (Blankenship & Mitchell (2006) Curr. Opin. Microbiol. 9:588-94). This cell population behaves as a continuous reservoir in the spread of infection. Additionally, it is resistant to many antifungal agents, as compared to planktonic cells (Seneviratne, et al. (2008) supra; Richard, et al. (2005) supra). The initiation of biofilm formation is dependent on the attachment of yeast cells to a substrate, which is followed by the attachment of yeast cells to each other (Granger, et al. (2005) Microbiology 151:1631-44). Adherence must extend to the hyphal layers. The agglutinin-like sequence (ALS) gene family is the largest family among known adhesins in C. albicans (Hoyer, et al. (1998) Curr. Genet. 33:451-9). It is known that ALS family members interact with several substrates, including host cells and proteins (Hoyer, et al. (2001) Trends Microbiol. 9:176-80; Sunstrom (2002) Cell Microbiol. 4:461-9; Kumamoto & Vinces (2005) Annu. Rev. Microbiol. 59:113-33). The finding that expression of ALS1 and other family members increases during biofilm development in vitro suggested that the ALS family plays a role in biofilm formation (Chandra, et al. (2001) J. Bacteriol. 183:5385-94; Green, et al. (2004) Microbiology 150:267-76; O'Connor, et al. (2005) Mol. Cell Probes 19:153-62). Hyphal wall protein 1 (HWP1), another adhesion gene, is also upregulated during biofilm development (Garcia-Sanchez, et al. (2004) Eukaryot. Cell 3:536-45). HWP1, a glycosylphosphatidylinositol-linked mannoprotein like the ALS proteins, is the best-characterized hyphal adhesin (Sundstrom (2002) supra; Staab, et al. (2004) J. Biol. Chem. 279:40737-47). It is a substrate for transglutaminase activity derived from a host, and thus it mediates covalent attachment of C. albicans to host cells (Sundstrom (2002) supra; Staab, et al. (1999) Science 283:1535-8).
The regulation of morphology-specific gene expression is a poorly understood process that is critical for the ability of C. albicans to adapt to and invade human hosts. However, a 368-bp region of the HWP1 promoter, designated the HWP1 control region (HCR), has been shown to be critical for activation under hypha-inducing conditions and confer developmental regulation to a heterologous ENO1 promoter (Kim, et al. (2007) Eukaryot. Cell 6(4):693-709).
Although there are many studies in the literature investigating pathogenic Candida, antifungal resistance, and virulence factors of Candida (Richard, et al. (2005) supra; Hoyer, et al. (1998) supra; Green, et al. (2004) supra; Hailis, et al. (2006) BMC Mol. Biol. 4:25; Candevir, et al. (2011) Turk. J. Med. Sci. 41:137-147; Evci, et al. (2010) Turk. J. Med. Sci. 40:141-9), new targets and approaches toward preventing or managing oral candidiasis are needed.